This project is intended to develop a protease inhibitor that can be safely administred to patients who have ongoing elastin destruction as a major feature of their disease. Such diseases include those in which phagocyte action (inflammation) has occurred in conjunction with connective tissue targets. Prominent among these diseases are pulmonary emphysema, pneumonias, adult respiratory distress syndrome, dermatologic inflammatory processes and infections, vasculititis, and autoimmune disorders. We have already demonstrated a unique inhibitor of human neutrophil elastase in several bacterial species. We have performed preliminary purification and characterization of one of these inhibitors. We must now document that this inhibitor is capable of preventing some of the diseases mentioned, in laboratory animal studies and, at the same time, document the safety of administration of this inhibitor. After the efficacy and safety of this product is documented in animal studies, application will be made to begin human studies. During Phase I, we hope to begin and complete the substantial portion of our animal studies using rabbit and rat experimental models of disease. Primarily, we will study the ability of this inhibitor to prevent experimentally induced emphysema and to mitigate against the permeability changes in animal models of the adult respiratory distress syndrome. During Phase II, further animal studies will be added and human studies will begin. If all the potential of this product is realized, then this medication may become the mainstay of therapy in millions of individuals in this country and around the world, several of which have no effective therapy.